Morbidity and mortality of coronavirus disease 2019 (COVID-19) are due in large part to severe cytokine storm and hypercoagulable state brought on by dysregulated host-inflammatory immune response, ultimately leading to multi-organ failure. Exacerbated oxidative stress caused by increased levels of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) along with decreased levels of interferon α and interferon β (IFN-α, IFN-β) are mainly believed to drive the disease process. Based on the evidence attesting to the ability of glutathione (GSH) to inhibit viral replication and decrease levels of IL-6 in human immunodeficiency virus (HIV) and tuberculosis (TB) patients, as well as beneficial effects of GSH on other pulmonary diseases processes, we believe the use of liposomal GSH could be beneficial in COVID-19 patients. This review discusses the epidemiology, transmission, and clinical presentation of COVID-19 with a focus on its pathogenesis and the possible use of liposomal GSH as an adjunctive treatment to the current treatment modalities in COVID-19 patients.

Abstract Abstract AIM: To describe the significant over-expression of fibroblast growth factor receptor 3 (FGFR3), which is a signal transduction and cell proliferation related gene in hepatocellular carcinoma (HCC). METHODS:Following DNA microarray, Northern blot and quantitative real-time PCR were employed to confirm FGFR3 expression difference in HCC tissues and surrounding non-neoplastic liver tissue. FGFR3 expression levels were further determined by immunohistochemical study in 43 cases of HCC. RESULTS:Northern blot results showed the significant over-expression of FGFR3 in HCC tissues, which was consistent with that from DNA microarray. Quantitative real-time PCR demonstrated that the mean ratio of FGFR3 mRNA to glyceraldehyde-3-phosphate dehydrogenase (GADPH) mRNA in HCC tissue was 0.250, whereas the ratio in non-neoplastic liver tissue was 0.014. Statistical analyses of 43 cases of HCC revealed that HCC scored higher than the matched non-neoplastic liver tissues. Examination of clinicopathological features revealed a strong correlation of over-expression of FGFR3 with poor tumor differentiation and high nuclear grade. CONCLUSION:Over-expression of FGFR3 may play an important role in liver carcinogenesis. FGFR3 may be an ideal candidate as a molecular marker in the diagnosis of HCC and a potential therapeutic target.

Background Previous reports have revealed inadequate resident education and textbook representation of dermatological conditions in patients with skin of color (SoC). This suggests that the literature and continuing medical education are important alternative dermatology educational resources to aid in diagnosing and treating patients of color. Objective This study develops criteria to assess and examine the prevalence of SoC-related publications among top dermatology journals. Methods We developed the first-ever prespecified criteria that allow for the assessment of diversity in the dermatologic literature. The archives of 52 dermatology journals from January 2018 to October 2020, selected based on Scopus ranking, were analyzed for journal characteristics and content regarding skin and hair of color, diversity and inclusion, and socioeconomic/health care disparities that affect underrepresented populations with SoC. Results Our study reveals that the average percentage of overall publications relevant to SoC is quite low. The percent of SoC articles ranged from 2.04% to 16.8% with a mean of 16.3%. The top-performing dermatology journals in SoC were, not surprisingly, from countries with populations with SoC; however, the Journal of Cosmetic and Laser Therapy, Australasian Journal of Dermatology , and Journal of the American Academy of Dermatol Case Reports were among the top 10. Research and higher-impact journals were among the lowest in SoC rankings, including the Journal of Investigative Dermatology, Experimental Dermatology , and Journal of the American Academy of Dermatology , and had <5% of articles on SoC. Conclusion We believe that the criteria we established could be used by journal editors to include at least 16.8% of SoC-relevant articles in each issue. Increasing SoC content in the dermatological literature, and particularly in high-impact journals, will serve as an invaluable educational resource and aid in promoting excellence in the care of patients with SoC.

Squamous cell carcinoma in situ (SCCIS) is a prevalent precancerous lesion that can progress to cutaneous squamous cell carcinoma. Although SCCIS is common, its pathogenesis remains poorly understood. To better understand SCCIS development, we performed laser captured microdissection of human SCCIS and the adjacent epidermis to isolate genomic DNA and RNA for next-generation sequencing. Whole-exome sequencing identified UV-signature mutations in multiple genes, including NOTCH1e3 in the epidermis and SCCIS and oncogenic TP53 mutations in SCCIS. Gene families, including SLFN genes, contained UV/oxidativesignature disruptive epidermal mutations that manifested positive selection in SCCIS. The frequency and distribution of NOTCH and TP53 mutations indicate that NOTCH mutations may precede TP53 mutations. RNA sequencing identified 1,166 differentially expressed genes; the top five enriched gene ontology biological processes included (i) immune response, (ii) epidermal development, (iii) protein phosphorylation, (iv) regulation of catalytic activity, and (v) cytoskeletal regulation. The NEURL1 ubiquitin ligase, which targets Notch ligands for degradation, was upregulated in SCCIS. NEURL1 protein was found to be elevated in SCCIS suggesting that increased levels could represent a mechanism for downregulating Notch during UV-induced carcinogenesis. The data from DNA and RNA sequencing of epidermis and SCCIS provide insights regarding SCCIS formation.

Non-melanoma skin cancers are cutaneous malignancies representing the most common form of cancer in the United States. They are comprised predominantly of basal cell carcinomas and squamous cell carcinomas (cSCC). The incidence of cSCC is increasing, resulting in substantial morbidity and ever higher treatment costs; currently in excess of one billion dollars, per annum. Here, we review research defining the molecular basis and development of cSCC that aims to provide new insights into pathogenesis and drive the development of novel, cost and morbidity saving therapies.

Tuberculosis (TB) remains a pervasive global health threat. A significant proportion of the world’s population that is affected by latent tuberculosis infection (LTBI) is at risk for reactivation and subsequent transmission to close contacts. Despite sustained efforts in eradication, the rise of multidrug-resistant strains of Mycobacteriumtuberculosis (M. tb) has rendered traditional antibiotic therapy less effective at mitigating the morbidity and mortality of the disease. Management of TB is further complicated by medications with various off-target effects and poor compliance. Immunocompromised patients are the most at-risk in reactivation of a LTBI, due to impairment in effector immune responses. Our laboratory has previously reported that individuals suffering from Type 2 Diabetes Mellitus (T2DM) and HIV exhibited compromised levels of the antioxidant glutathione (GSH). Restoring the levels of GSH resulted in improved control of M. tb infection. The goal of this review is to provide insights on the diverse roles of TGF- β and vitamin D in altering the levels of GSH, granuloma formation, and clearance of M. tb infection. We propose that these pathways represent a potential avenue for future investigation and development of new TB treatment modalities.

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and is associated with cumulative UV exposure. Studies have shown that prolonged voriconazole use promotes cSCC formation; however, the biological mechanisms responsible for the increased incidence remain unclear. Here, we show that voriconazole directly increases oxidative stress in human keratinocytes and promotes UV‐induced DNA damage as determined by comet assay, 8‐oxoguanine immunofluorescence and mass spectrometry. Voriconazole treatment of human keratinocytes potentiates UV‐induced apoptosis and activation of the p38 MAP kinase and 53BP1 UV stress response pathways. The p38 MAP kinase activation promoted by voriconazole exposure can be mitigated by pretreating keratinocytes with N‐acetylcysteine. Voriconazole increases oxidative stress in keratinocytes by directly inhibiting catalase leading to lower intracellular NADPH levels and the triazole moieties in voriconazole are critical for inhibiting catalase. Furthermore, voriconazole is shown to promote UV‐induced dysplasia in an in vivo model. Together, these data demonstrate that voriconazole potentiates oxidative stress in UV‐irradiated keratinocytes through catalase inhibition. Use of antioxidants may mitigate the pro‐oncogenic effects of voriconazole.

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